Phase 1 Open-label Study of the Absorption, Metabolism, and Excretion of Poziotinib Following a Single Oral Dose of [14C]-Poziotinib in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[last]) of [14C]-Poziotinib, Metabolites M1 and M2
研究概览
简要总结
This will be a Phase 1, open-label, nonrandomized, single-dose study in healthy male subjects to evaluate the Absorption, Metabolism, and Excretion of Poziotinib following a single oral dose of [14C]-poziotinib to healthy male subjects.
详细描述
Potential subjects will be screened to assess their eligibility to enter the study within 28 days prior to the dose administration. Subjects will be admitted into the Clinical Research Unit (CRU) on Day -1. On the morning of Day 1, all subjects will receive a single oral dose of 8 mg (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib in the fasted state.
Subjects will be confined to the CRU until at least Day 8.
Subjects will be discharged from the CRU on Day 8 if the following criteria are met:
- ≥90% mass balance recovery in combined urine and feces, and
- ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in 2 consecutive 24-hour periods in which fecal and urine samples are obtained.
If these criteria are not met by Day 8, subjects will remain in the CRU until all discharge criteria are met up to a maximum of Day 15 in order to continue 24-hour blood, urine, and feces collections, unless otherwise agreed upon by the Sponsor and Investigator.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Body mass index between 18.0 and 32.0 kg/m2, inclusive
- •In good health at Screening and/or at Check-in
- •Subjects must be surgically sterile for at least 90 days, or when sexually active with female partners of childbearing and non-childbearing potential will be required to use a male condom with spermicide from CRU Check-in until 90 days after discharge. Subjects are required to refrain from donation of sperm from CRU Check-in until 90 days after discharge
- •Able to comprehend and willing to sign an ICF and to abide by the study restrictions
- •History of at least 1 bowel movement per day
排除标准
- •Stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs
- •Swallowing difficulties or ongoing diarrhea of any etiology
- •Participation in a clinical study involving an investigational drug in the past 30 days prior to dosing
- •Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to Check-in
- •Use or intend to use any prescription medications/products within 14 days prior to Check-in
- •Use or intend to use slow-release medications/products considered to still be active within 14 days prior to Check-in
- •Exposure to significant diagnostic or therapeutic radiation or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in
研究组 & 干预措施
Poziotinib
A single oral dose of 8 mg poziotinib as a capsule formulation (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib
干预措施: [14C]-Poziotinib (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[last]) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
Maximum Observed Plasma Concentration (Cmax) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
Tmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
AUC(inf) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
Cmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
Time to Attain Maximum Observed Plasma Concentration (Tmax) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
AUC(last) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
Percentage of AUCinf Derived by Extrapolation (%AUCext) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
%AUCext of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
λz, or kel of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
Apparent Terminal Elimination Half-Life (t1/2) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
Total Radioactivity of Cumulative Amount Excreted in Feces (Aef)
时间窗: 1-15 days
Total Radioactivity of Fraction of Dose Excreted in Urine and Feces (fetotal)
时间窗: 1-15 days
t1/2 of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
时间窗: 1-15 days
Elimination Rate Constant (λz, or kel) of [14C]-Poziotinib, Metabolites M1 and M2
时间窗: 1-15 days
Apparent Volume of Distribution (VZ/F) During Terminal Phase of [14C]-Poziotinib
时间窗: 1-15 days
Apparent Oral Clearance (CL/F) of [14C]-Poziotinib
时间窗: 1-15 days
Whole Blood : Plasma Concentration Ratios of Total Radioactivity of [14C]-Poziotinib
时间窗: 1-15 days
Total Radioactivity of Cumulative Amount Excreted in Urine (Aeu)
时间窗: 1-15 days
Total Radioactivity of Fraction of Dose Excreted in Urine (feu)
时间窗: 1-15 days
Total Radioactivity of Fraction of Dose Excreted in Feces (fef)
时间窗: 1-15 days
Total Radioactivity of Cumulative Total Amount Excreted (Aetotal)
时间窗: 1-15 days
Poziotinib Metabolite Profiling and Identification in Plasma
时间窗: 1-15 days
次要结局
- Number of Participants with Hematology, Clinical Chemistry, Urinalysis Laboratory Abnormalities(1-15 days)
- Number of Participants with 12-lead electrocardiograms (ECG) Abnormalities(1-15 days)
- Number of Participants with Vital Sign and Physical Examinations Abnormalities(1-15 days)
- Number of Participants with Adverse Events (AEs)(1-15 days)